Real-Life Benefit and Costs of First Line Pembroli-zumab for Advanced NSCLC—A Propensity-Score Matched Case-Control Study

Background: Immune checkpoint inhibitor (ICI) therapy using Pembrolizumab alone or in combina-tion with chemotherapy (CHT) is a widely used first-line standard for advanced NSCLC without ac-tionable driver mutations. However, a considerable fraction of patients does not respond to ICI, and associated costs are significant. We aimed to investigate the real-life benefit and costs of first line Pembrolizumab as compared to a matched historical cohort treated with first-line CHT in the pre-ICI era. Methods: Ninety-three subsequent patients having received first-line pembrolizumab as mono-therapy (n=17) or together with platinum-based doublet CHT (n=76) between 2017 and 2021 were retrospectively identified. Using propensity-score matching for age, sex, Eastern Co-operative of On-cology Group (ECOG) performance status and histological subtype, the ICI-treated cohort was com-pared to a historical NSCLC cohort treated with first-line platinum-based doublet CHT between 2011 and 2014, whereas patients who had received ICI in later therapy lines were excluded. Progres-sion-free (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method; the log-rank test was used for statistical comparison between the cohorts. Therapy costs were calculated based on the respective average drug prizes between 2017 and 2019 for both treatment groups. Results: Both cohorts did not significantly differ in terms of matching criteria. Among the patients treated with first line pembrolizumab, median PFS was 6 months (M) (95% confidence interval (CI) 4-9) and signifi-cantly longer (p<0.001) than in the historical CHT cohort (4M; 95% CI 3-5). Similarly, median OS was significantly longer in the ICI group (14M (95% CI 8-19) vs. 8M (95% CI 7-10); p=0.01). Total therapy costs were €3,635,572 in the ICI and €867,000 in the CHT cohort, respectively, average costs per pa-tient were €39,092 and €8,179. Incremental cost-effectiveness ratio (ICER) per month of median OS gained was €5,152. Conclusion: Patients with advanced NSCLC treated with first-line pembroli-zumab had significantly longer PFS and OS as compared to historical fist-line CHT patients. Howev-er, this benefit was associated with considerably higher treatment costs.